Association between Toll-Like Receptor 3 (TLR3) rs3775290, TLR7 rs179008, TLR9 rs352140 and Chronic HCV.

BACKGROUND: Inconsistent results were reported on the association of TLRs polymorphisms with the risk of HCV infection and HCV-related diseases. OBJECTIVE: to assess the relation between TLR3 rs3775290, TLR7 rs17900 and TLR9 rs352140 SNPs and chronic HCV in the Egyptian cohort and to study their relation to interferon response. METHODS: TLR3 rs3775290, TLR7 rs179008 and TLR9 rs352140 gene polymorphisms were typed by RFLP for 100 patients with chronic HCV and 25 with HCC in addition to 100 healthy controls. RESULTS: A significant higher frequency has been found for the CT genotype of TLR3 rs3775290 in chronic HCV infection (p < 0.001) and CC genotype and the combined genotype CC-AT-GA ♀ in controls (p < 0.001). Non-significant associations have been found for studied SNPs and HCC and response to interferon and also the viral load or the degree of fibrosis, however, the higher HCV viral load and the higher grade of fibrosis were associated with treatment failure (p < 0.001). CONCLUSION: The heterozygous CT genotype of TLR3 rs3775290 may be a susceptibility risk factor for chronic HCV infection and the homozygous CC and the combined CC-AT-GA ♀ genotypes may be protective. The HCV viral load and the grades of liver fibrosis could be considered a risk factor for interferon treatment failure. It seems that the studied SNPs have no role in HCC development or failure of treatment. However, the small sample size is a limiting factor of the present study when interpreting the negative associations and that the current used cohort does not permit such conclusion. ABBREVIATIONS: cHCV=chronic Hepatitis C virus, HCC=hepatocellular carcinoma, TLR=Toll like Receptor, RFLP=Restriction Fragment Length Polymorphism, SNP=Single Nucleotide Polymorphism, IFN-α= interferon alpha.

Toxoplasma gondii infection among chronic hepatitis C patients: a case-control study.

OBJECTIVE: To determine the detection rate of anti-Toxoplasma gondii (T. gondii) IgG and IgM in chronic HCV patients attending the Department of Tropical Medicine Mansoura University hospital in Egypt. METHODS: This study included 120 adult chronic HCV patients, 81 decompensate cirrhosis (late-stage) and 39 chronic HCV non cirrhotic patients (early-stage) and 40 healthy blood donors as controls. Serum samples were examined for anti-Toxoplasma IgM and anti-Toxoplasma IgG antibodies by ELISA. Real-time RT-polymerase chain reaction assay was done for quantitation of hepatitis C virus. RESULTS: Anti-T. gondii IgG antibodies were detected in 75 (92.6%) of 81 late-stage cirrhotic patients, 30 (76.9%) of the 39 chronic HCV non cirrhotic patients (early-stage) and in 6 (15%) of 40 controls with statistically significant difference (P<0.001). Anti-T. gondii IgM antibodies were found in 11 (13.6%) in late stage patients, 5 (12.8%) in early stage and in 3 (7.5%) of controls with no statistical significant difference (P=0.610). There was no correlation between stage of fibrosis and IgM or IgG antibodies positivity in our studied groups (P=0.526). High IgG levels significantly correlated with high viral load (P=0.026). CONCLUSIONS: Our findings suggest that the serious opportunistic T. gondii infection represent a potential significant risk for chronic HCV patients. So, toxoplasmosis should be considered in their investigations and follow-up.

Human leukocyte antigen class I alleles can predict response to pegylated interferon/ribavirin therapy in chronic hepatitis C Egyptian patients.

BACKGROUND: Racial differences and broad spectrum response to anti-hepatitis C (anti-HCV) therapy suggest a possible role for host genetic diversity in treatment outcomes. We aim to determine the association and predictive value of certain human leukocyte antigen (HLA) class I alleles with either susceptibility to viral clearance or persistence following pegylated interferon (Peg-IFN) plus ribavirin therapy in chronic hepatitis C (HCV) genotype 4 patients in Egypt.  METHODS: This study included 200 unrelated chronic HCV patients who received Peg-IFN plus ribavirin therapy [112 patients with sustained virological response (SVR) and 88 non-responders (NR)]. Serological testing of HLA class I antigens (HLA-A and HLA-B alleles) were performed by standard complement-dependent microlymphocytotoxicity assay.  RESULTS: The frequency of HLA-A01 was significantly higher in SVR than in NR cases [OR: 0.51; 95% CI: 0.27-0.981; P = 0.042], while the frequency of alleles B38 (P = 0.011), B40 (P < 0.001) and B41 (P < 0.001) was significantly higher in NR cases (OR/95% CI: 7.05/(1.39-18.01), 10.31/3.14-36.1 . On logistic regression analysis, presence of the HLA-A01 allele was associated with SVR  (OR: 0.50; 95% CI: 0.28-0.89; P = 0.02) and HLA-B38 can predict non response to therapy (OR: 7.92; 95% CI: 1.67-37.54; P = 0.009) with an overall accuracy of 60%.Severe fibrosis (OR: 3.035; 95% CI: 1.521-6.091; P = 0.002), high viremia (OR: 2.69; 95% CI: 1.11-6.53; P = 0.005) and steatosis (OR: 2.1; 95% CI: 1.002-3.90; P = 0.041) predicted no response with an overall accuracy of 81.8%.  CONCLUSION: HLA-A01 and HLA-B38 alleles are associated with and may have a role in the outcome of response to Peg-IFN plus ribavirin therapy in Egyptian patients diagnosed with chronic HCV infection. The use of immunologic markers to predict the outcome of treatment may help pharmacogenetic personalization of treatment for HCV infection.

Colorectal schistosomiasis: Is it still endemic in delta Egypt, early in the third millennium?

BACKGROUND: Several governmental efforts have been exerted toward controlling schistosomiasis during the last decades in Egypt. This work was designed to study the prevalence of colorectal schistosomiasis in patients with different gastrointestinal symptoms. MATERIALS AND METHODS: Patients presented to the gastroenterology unit with different gastrointestinal symptoms were endoscopically examined, where three to six tiny biopsies were taken from those with visible, suspected schistosomal lesions for histopathological examination and two additional rectal biopsies were taken from the apparently normal colonic mucosa. Form each patient, at least three stool samples were examined by the formal-ether concentration method for schistosoma ova. RESULTS: Colonic abnormalities were detected in 510 out of 984 patients presented with different gut symptoms. Schistosoma mansoni was detected in 205 patients (180 males, 25 females) with an age range (18-65years). Six patients only had schistosomal polyps and excised successfully by snare polypectomy. The squash technique established the diagnosis of schistosomiasis in all endoscopically normal 118 (50.75%) cases by demonstrating the schistosomiasis ova and their associated histopathological findings showed no or minimal reaction in 96 (46.82%) cases and variable degrees of submucosal granulomata in the remaining cases. Stool examination detected the schistosomiasis ova in 25 (9.83%) patients only of the biopsy-positive cases. CONCLUSIONS: Our data revealed that despite governmental efforts, the prevalence of colorectal schistosomiasis (20.83%) is significant among patients with gut symptoms. Gaps in health care services should be detected and filled appropriately.

Clinical significance of antibody to hepatitis B core antigen in multitransfused hemodialysis patients.

BACKGROUND: In spite of the progress made in the prevention of transfusion transmitted infections over the last few years, transmission of HBV infection through transfusion of HBsAg negative blood has been documented. OBJECTIVES: To assess the frequency and clinical significance of anti-HBc in multitransfused hemodialysis patients. MATERIALS AND METHODS: One hundred and forty-three hemodialysis patients who had been receiving blood regularly with an average of 39.4 +/- 7.579 months on hemodialysis were enrolled in this study. HBV markers (HBsAg, anti-HBc, anti-HBs) were measured in these patients and in 100 healthy controls by the ELISA technique. The following data were obtained for all patients: socio demographic data, number of blood transfusions and some laboratory investigations. RESULTS: In our patients, anti-HBc was positive in 9%, anti HBs in 7%, coexistant HbsAg/anti-HBc in 2.8% and anti HBc/anti HBs in 18.9%, meanwhile no patients were positive for HBsAg alone. In patients with only positive anti-HBc, the levels of anti-HBc were significantly related to abnormal results of liver function. In patients with positive anti-HBs/anti-HBc (n = 27), 18 patients had abnormal liver function, and 9 patients had normal liver function with no significant difference between them. CONCLUSIONS: This study suggests that hepatitis B prevalence in our multitransfused hemodialysis patients is far in excess of that anticipated on the basis of HBsAg prevalence. Absence of HBsAg in the blood of hemodialyzed patients may not be sufficient to ensure lack of circulating HBV, and isolated positivity of anti-HBc may be a possible indicator of active hepatitis B infection.

Study of some immune aspects in patients with fascioliasis before and after Chommiphora molmol (Mirazid) treatment.

This study was planned to evaluate the in vitro production of IL-1 beta and IL-4 by peripheral blood mononuclear cells (PBMCs) and total IgE in patients with fascioliasis before and 3 months after treatment with purified extract of myrrh from Commiphora molmol tree (Mirazid), to determine the role of these variables in immunopathogenesis of the disease in relation to this new drug. The study was carried out in Departments of Tropical Medicine, Al-Azhar University Hospitals in the period from March 2002 to November 2003. A total of 35 patients with chronic fascioliasis with age range from 9-45 years in addition to 10 healthy subjects with matched age and sex serving as controls were studied. Serum IgE and in vitro IL-1 and IL-4 were estimated by enzyme immuno-assay (ELISA) before and 3 months after therapy. Results revealed significant increase in IL-1 beta in patients before treatment than control (p<0.001) but it decreased significantly after therapy (p<0.001) to reach the control level (p=0.16). In contrast, IL-4 was significantly lower than control before therapy (p=0.04) and increased significantly after treatment (p<0.001) to reach normal levels as control (p=0.59). Total IgE was significantly elevated in patients before treatment (p<0.001) and it did decrease significantly with treatment (p<0.001), although it remained significantly higher than the control level. In conclusion, Mirazid is an effective fasciolicidal drug. IL-1 may be involved in disease immunopathogenesis and the depressed IL-4 may be a phenomenon of parasite immune suppression. Complete decline of total IgE is not an early criterion of cure.